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基于模型的生物反应器分析与优化及其在造血干细胞培养中的应用。

Model-based analysis and optimization of bioreactor for hematopoietic stem cell cultivation.

机构信息

Bioprocess and Microbiology Laboratory, Department of Chemical Engineering, Faculty of Industrial Technology, Bandung Institute of Technology, Ganesha 10, Bandung 40132, Indonesia.

出版信息

Bioprocess Biosyst Eng. 2011 Jan;34(1):81-93. doi: 10.1007/s00449-010-0449-z. Epub 2010 Jul 23.

Abstract

One of the problems to be solved in attaining the full potentials of hematopoietic stem cell (HSC) applications is the limited availability of the cells. Growing HSCs in a bioreactor offers an alternative solution to this problem. Besides, it also offers the advantages of eliminating labour intensive process as well as the possible contamination involved in the periodic nutrient replenishments in the traditional T-flask stem cell cultivation. In spite of this, the optimization of HSC cultivation in a bioreactor has been barely explored. This manuscript discusses the development of a mathematical model to describe the dynamics in nutrient distribution and cell concentration of an ex vivo HSC cultivation in a microchannel perfusion bioreactor. The model was further used to optimize the cultivation by proposing three alternative feeding strategies in order to prevent the occurrence of nutrient limitation in the bioreactor. The evaluation of these strategies, the periodic step change increase in the inlet oxygen concentration, the periodic step change increase in the media inflow, and the feedback control of media inflow, shows that these strategies can successfully improve the cell yield of the bioreactor. In general, the developed model is useful for the design and optimization of bioreactor operation.

摘要

在充分发挥造血干细胞(HSC)应用潜力的过程中,需要解决的问题之一是细胞的可用性有限。在生物反应器中培养 HSC 为解决这个问题提供了一种替代方案。此外,它还具有消除劳动密集型过程以及传统 T 瓶干细胞培养中定期营养补充所涉及的潜在污染的优点。尽管如此,生物反应器中 HSC 培养的优化几乎没有被探索过。本文讨论了开发一种数学模型的方法,以描述在微通道灌注生物反应器中体外 HSC 培养的营养分布和细胞浓度的动态。该模型进一步用于通过提出三种替代喂养策略来优化培养,以防止生物反应器中出现营养限制。对这些策略的评估,即入口氧气浓度的周期性阶跃增加、培养基流入的周期性阶跃增加以及培养基流入的反馈控制,表明这些策略可以成功提高生物反应器的细胞产量。总的来说,所开发的模型对于生物反应器操作的设计和优化是有用的。

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